TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17746	53461;53462;53463	chr2:178607452;178607451;178607450	chr2:179472179;179472178;179472177
N2AB	16105	48538;48539;48540	chr2:178607452;178607451;178607450	chr2:179472179;179472178;179472177
N2A	15178	45757;45758;45759	chr2:178607452;178607451;178607450	chr2:179472179;179472178;179472177
N2B	8681	26266;26267;26268	chr2:178607452;178607451;178607450	chr2:179472179;179472178;179472177
Novex-1	8806	26641;26642;26643	chr2:178607452;178607451;178607450	chr2:179472179;179472178;179472177
Novex-2	8873	26842;26843;26844	chr2:178607452;178607451;178607450	chr2:179472179;179472178;179472177
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-113
• Domain position: 70
• Structural Position: 158
• Q(SASA): 0.1774
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
A/T	rs886055266	None	0.989	D	0.667	0.683	0.68099412893	gnomAD-4.0.0	1.59247E-06	None	None	None	None	I	None	0	0	None	0	2.77716E-05	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
A/C	0.8721	likely_pathogenic	0.8495	pathogenic	-1.16	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
A/D	0.997	likely_pathogenic	0.9973	pathogenic	-1.749	Destabilizing	0.998	D	0.809	deleterious	D	0.636678975	None	None	I
A/E	0.9941	likely_pathogenic	0.9945	pathogenic	-1.786	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
A/F	0.9868	likely_pathogenic	0.9808	pathogenic	-1.182	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	I
A/G	0.3255	likely_benign	0.3357	benign	-1.206	Destabilizing	0.217	N	0.353	neutral	D	0.545034659	None	None	I
A/H	0.9983	likely_pathogenic	0.9979	pathogenic	-1.375	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
A/I	0.9064	likely_pathogenic	0.8663	pathogenic	-0.463	Destabilizing	0.995	D	0.762	deleterious	None	None	None	None	I
A/K	0.9989	likely_pathogenic	0.9988	pathogenic	-1.242	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	I
A/L	0.8279	likely_pathogenic	0.7813	pathogenic	-0.463	Destabilizing	0.983	D	0.657	neutral	None	None	None	None	I
A/M	0.944	likely_pathogenic	0.9187	pathogenic	-0.393	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
A/N	0.9946	likely_pathogenic	0.9945	pathogenic	-1.052	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	I
A/P	0.9954	likely_pathogenic	0.9942	pathogenic	-0.591	Destabilizing	0.999	D	0.79	deleterious	D	0.62045781	None	None	I
A/Q	0.9923	likely_pathogenic	0.9922	pathogenic	-1.266	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
A/R	0.9956	likely_pathogenic	0.995	pathogenic	-0.879	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
A/S	0.5238	ambiguous	0.5214	ambiguous	-1.35	Destabilizing	0.989	D	0.583	neutral	D	0.584997339	None	None	I
A/T	0.7403	likely_pathogenic	0.7061	pathogenic	-1.303	Destabilizing	0.989	D	0.667	neutral	D	0.619852397	None	None	I
A/V	0.6428	likely_pathogenic	0.5674	pathogenic	-0.591	Destabilizing	0.733	D	0.387	neutral	N	0.50087202	None	None	I
A/W	0.9992	likely_pathogenic	0.9989	pathogenic	-1.515	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
A/Y	0.996	likely_pathogenic	0.9946	pathogenic	-1.118	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.